Elizabeth A. Stewart Lab

These models help illuminate the biologic characteristics and mechanisms that may play roles in recurrent disease, in particular the specific cell populations that tend to survive chemotherapy and later cause a patient’s cancer to recur. Our preclinical models, coupled with advanced analytical techniques, lead to a better understanding of tumor heterogeneity in recurrent tumors. 

To underscore the importance of tumor heterogeneity in our line of research, our lab is using patient-derived xenografts to generate 2D and 3D in vitro models of pediatric solid tumors. These models maintain tumor heterogeneity, an important differentiator from traditional cells lines that often become homogeneous over time and therefore may lose some cell population that are critical in the recurrence of solid tumors. 

As information continues to emerge about certain cancer drug combinations, or as targeted drugs become available, our lab vigorously tests these drugs in our preclinical models to prioritize novel therapeutic agents that can be further tested in clinical trials. As an example of the success of this approach, our lab discovered that a class of drugs called PARP inhibitors for Ewing sarcoma led to a better response in our preclinical models when used in combination with chemotherapy. The results of that discovery were later translated into several clinical trials, and follow-up studies are currently being explored in the lab.

The research in our lab has led to the largest collection of well-characterized pediatric solid tumor models and data, which is freely available to investigators around the globe through the Childhood Solid Tumor Network at St. Jude. To date, the network has shared resources generated by our lab with more than 100 different institutions and investigators to advance the study of pediatric solid tumors of multiple histologies.

The core of our laboratory’s work strives to discover insights and share information that fuels further research to advance the understanding of recurrent solid tumors in children.